Part I Overview Information

Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)

Components of Participating Organizations
National Institute of Mental Health (NIMH), (http://www.nimh.nih.gov)

Title: Neurodevelopment and Neuroendocrine Signaling in Adolescence: Relevance to Mental Health (R21)

Announcement Type
This is a reissue of PA-05-162, which was previously released September 1, 2005, and now is listed as a separate FOA for the R21 funding mechanism.

Update: The following update relating to this announcement has been issued:

• October 8, 2008 - This PA has been reissued as (PA-09-009).
• September 17, 2007 - Expiration Date adjusted to accommodate recent changes to standing submission deadlines, per NOT-OD-07-093.

NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide.

APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply).

A registration process is necessary before submission and applicants are highly encouraged to start the process at least four weeks prior to the grant submission date. See Section IV.

Key Dates
Release/Posted Date: May 19, 2006
Opening Date: May 19, 2006 (Earliest date an application may be submitted to Grants.gov).
NOTE: On time submission requires that applications be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization)
Application Submission Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm
Peer Review Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Council Review Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Earliest Anticipated Start Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Additional Information To Be Available Date (URL Activation Date): Not Applicable
Expiration Date: July 2, 2009 (Now Expired October 8, 2008 per PA-09-009)
(now September 8, 2009 per NOT-OD-07-093)

Due Dates for E.O. 12372
Not Applicable

Additional Overview Content

Executive Summary

• This funding opportunity announcement (FOA) solicits Exploratory/Developmental (R21) grant applications from applicant organizations that propose to identify neurodevelopmental and neuroendocrine mechanisms that impact emotional and cognitive development and emerging psychopathology during adolescence, utilizing animal models and human studies.
• This FOA runs in parallel with an FOA of identical scientific scope, PA-05-162, that solicits R01 research grant applications.
• Awards issued under this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications. The total amount awarded and the number of awards will depend upon the mechanism numbers, quality, duration, and costs of the applications received.
• Budget and Project Period: The total project period for an application submitted in response to this funding opportunity may not exceed two years. Direct costs are limited to $275,000 over an R21 two-year period, with no more than $200,000 in direct costs allowed in any single year.
• Eligible organizations: For profit organizations; Non-profit organizations; public or private institutions, such as universities, colleges, hospitals and laboratories; units of State and local governments; eligible agencies of the Federal government; domestic or foreign institutions/organizations; faith-based or community-based organizations; Indian/Native American Tribal Government (Federally Recognized); Indian/Native American Tribal Government (Other than Federally Recognized); and Indian/Native American Tribally Designated Organization
• Eligible Project Directors/Principal Investigators (PDs/PIs): Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
• Applicants may submit more than one application, provided each application is scientifically distinct.
• See Section IV.1 for application materials. The SF424 (R&R) Application Guide for this FOA is located at these Web sites:
  • http://grants1.nih.gov/grants/funding/424/SF424_RR_Guide_General_Ver2.doc (MS Word)
  • http://grants1.nih.gov/grants/funding/424/SF424_RR_Guide_General_Ver2.pdf (PDF)
• For general information on SF424 (R&R) Application and Electronic Submission, see these the following Web sites:
  • SF424 (R&R) Application and Electronic Submission Information: http://grants.nih.gov/grants/funding/424/index.htm
• General information on Electronic Submission of Grant Applications: http://era.nih.gov/ElectronicReceipt/
• Telecommunications for the hearing impaired is available at: TTY 301-451-5936.
• Initial merit review convened by the CSR

Table of Contents

Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

Section II. Award Information
1. Mechanism of Support
2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2. Cost Sharing or Matching
3. Other - Special Eligibility Criteria

Section IV. Application and Submission Information
1. Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Submission, Review, and Anticipated Start Dates
1. Letter of Intent
B. Submitting an Application Electronically to the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Sharing Research Data
D. Sharing Research Resources
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
3. Reporting

Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

Section I. Funding Opportunity Description

1. Research Objectives

Background

Adolescence is a developmental period encompassing dramatic hormonal, physiological, and behavioral change. It is also a uniquely important period for brain and psychological development during which the symptoms of several mental disorders such as depression, schizophrenia, eating disorders, and substance abuse are often first reported. This raises questions of both moderating and mediating factors, as well as opportunities for prevention and early treatment. A thorough understanding of developmental neurobiology will help address these critical health issues. To date, however, little is known about the underlying genetic, molecular and neurochemical systems that mediate changes in the brain, or the degree to which hormonal signals initiate neurodevelopmental and behavioral changes during adolescence.

Complicating our understanding of the developmental neurobiology of adolescence are sociocultural influences and considerable variability in the age and rate at which individuals undergo pubertal development. Pubertal changes occur earlier than previously and now generally span ages 9 to 15 years. Early puberty in girls and late puberty in boys constitute risk factors for adjustment problems. Which changes in brain and behavior emerge as a function of chronological age and which emerge as a function of puberty, and specifically, hormonal effects on brain, are empirical questions.

Recent NIMH-sponsored workshops reviewed research in the area of neuroendocrinology and neurodevelopment relevant to adolescence and adolescent psychopathology. Several areas of research opportunity were identified. This initiative encourages basic and translational research targeted toward improved understanding of adolescent brain development and the neurobiological processes that may contribute to risk for mental disorders during this period; the identification of appropriate targets to reduce risk; and the potential development of preventive and treatment interventions. Basic research aimed at identifying neurobiological changes in brain regions and circuits involved in emotional and cognitive processes (emotional regulation, executive functions, reward sensitivity and decision making) including, for example, the amygdala, hippocampus, bed nucleus of the stria terminalis, and prefrontal cortex, is strongly encouraged. The relative lack of appropriate cellular, molecular and genetic tools has limited progress towards identifying neuroendocrine factors contributing to juvenile brain development. Therefore, this initiative also supports the development of novel approaches to assess, visualize, and manipulate dynamic neuroendocrine signaling processes in brain that contribute to alterations in emotional and cognitive function during adolescence. The development and validation of model systems for exploring the impact of specific hormonal changes in species that adequately mimic aspects of human neuroendocrine function is also specifically encouraged. In order to parse the relationships between brain development and hormonal function in puberty and across adolescence, the search for neuroendocrine regulators of adolescent brain function must occur in parallel with broader research efforts to identify the multiple neurodevelopmental changes occurring in both sexes during this period. Thus, this initiative encourages the expansion of basic developmental neurobiological and behavioral studies into adolescence. Studies in normal human adolescents and clinical populations are encouraged to explore neurodevelopmental, neuroendocrine, behavioral, and environmental processes contributing to changes in cognitive and affective regulation, the expression of symptoms of psychopathology during this period, and the identification of potential targets for preventive and treatment interventions.

Research Scope

The purpose of this initiative is to encourage research that will identify neurodevelopmental, molecular, and hormonal changes that are critical in altering emotional and cognitive development during adolescence. It is expected that this research will contribute to understanding of normal developmental processes and will help identify potential targets contributing to psychopathology in adolescence, including targets for the development of preventive or treatment interventions. The FOA encourages both basic neurobiological studies in model systems as well as studies in normal adolescent humans and in clinical populations. Studies aimed at identifying the molecular signals regulating the onset of puberty are not appropriate for this solicitation. However, studies focusing upon the impact of these signals in brain systems regulating cognitive and emotional processes are appropriate. Research with implications for the development of targeted intervention strategies is of particular interest.

Listed below are examples of areas of interest. Research relevant to this FOA is not limited to these examples.

Adolescent brain neurobiology:

• Define molecular and cellular mechanisms regulating neural atrophy, pruning, and growth across adolescence and delineate how these processes impact brain function and behavior in model systems relevant to mental illness.
• Characterize and define alterations in glial biology during adolescent brain development and examine the specific roles of glial subpopulations (astrocytes, oligodendrocytes and microglia) in modifying developmental pathways and functional brain activity.
• Identify genetic, epigenetic, and experiential factors that modulate anatomical and molecular brain changes during adolescence.
• Identify molecular and electrophysiological signaling changes in circuits implicated in mood disorders and mood regulatory processes across adolescence.
• Apply cellular and systems mapping techniques (both in vivo and in vitro) to identify changes in neural organization and connectivity during adolescent brain development. Areas of critical focus include neural circuitry and systems integration in brain areas involved in emotional and cognitive processes such as the amygdala, hippocampus, bed nucleus of the stria terminalis, and prefrontal cortex.
• Apply conditional mutagenesis strategies to explore the impact of molecular factors on developmental trajectories in adolescence.

Developmental Neuroendocrinology:

• Delineate the expression of hormone signaling molecules (nuclear and membrane receptors, binding proteins, signaling components) in brain throughout adolescence.
• Examine the impact of normal and disordered hormonal changes (gonadal, adrenal, growth) on neurodevelopmental processes, including behavior, in appropriate model systems and human conditions.
• Examine the role of hormones in determining sex and age-related differences in basic neural signaling, neuronal and behavioral responses to stressors, and psychotherapeutic drug response.
• Identify mechanisms whereby gonadal steroids (i.e., estrogen, progesterone, androgens) and neurosteroids modulate neurotransmitter systems implicated in mood regulation (e.g., NE, DA, 5-HT, GABA) across adolescence.

Environmental sensitivity of adolescence:

• Characterize developmental changes in brain and behavioral stress responses (including stressor-specific changes) and the relative persistence of exposure effects from peri-adolescence into adulthood. Identify neurobiological and hormonal mediators of these changes.
• Assess whether adolescence represents a period of unique sensitivity to experiential factors modulating the development of emotional circuits in adulthood.
• Determine whether specific brain regions have different critical periods across adolescence.
• Identify circumstances under which hormone exposure (or lack thereof) during adolescence has unique effects on the development of neural circuitry and behavior.
• Examine effects of early life events (e.g., pre- and early post-natal experiences) on neural changes induced by hormonal or environmental change in adolescence and identify mechanisms through which such interactions occur.

Sex differences:

• Distinguish hormone-dependent from non-hormone, sex-determined and other neurodevelopmental effects in adolescence.
• Distinguish genetic effects of sex chromosomes from organizational and activational effects of gonadal hormones on brain development and behavioral plasticity related to mood and cognition.

Technology development and novel tool application opportunities:

• Apply selective ligands and genetic tools to examine the impact of manipulating aspects of neuroendocrine signaling during defined developmental windows.
• Apply molecular techniques to identify neural genes whose expression is sensitive to hormonal changes across adolescence.
• Develop novel PET ligands and other approaches for imaging changes in gonadal and neurosteroid hormone receptor expression and activation in brain.
• Develop sensitive and selective cellular markers to detect changes in adolescent brain development.
• Develop novel ligands that target specific hormone receptors for research.
• Develop novel molecular and genetic tools and approaches for neuroendocrine and molecular studies of adolescence including gene trapping, conditional mutagenesis, and improved cellular and molecular markers.
• Apply brain imaging (functional MRI, DTI, PET, SPECT, MRS, MRS imaging [MRSI]) to identify circuits and molecules that mediate behavioral change in adolescence in model systems and humans where applicable.
• Develop techniques requiring little or no radiation exposure for human studies in children ages 9 through 18 years of age to overcome the limitations posed by the low radiation safety guidelines for minors that frequently preclude the use of PET/SPECT for receptor occupancy studies.
• Develop improved MR-based techniques (e.g., MRS, MRS imaging (MRSI), functional MRI), such as quantitative techniques that may offer greater reliability for longitudinal studies of development (e.g., arterial spin labeling; high sensitivity MRS/MRSI).
• Develop and validate fMRI paradigms to evaluate the functional integrity of neurocircuitry underlying emotional regulation, executive functions, reward sensitivity, decision making and other domains known to be affected in adolescent mental disorders.
• Technology development applications need not be hypothesis driven. Applications developing new technologies should validate the technologies before using them to test novel hypotheses related to brain or behavior.

Unique opportunities for understanding neural mechanisms regulating behavioral change in adolescence:

• Expand models to identify critical genes, molecules, and circuits underlying changes in cognitive and emotional function (including, for example, fear, anxiety, depression) across adolescent development.
• Integrate genetic and systems neurobehavioral models to examine possible functional relationships between molecules involved in the initiation of puberty (such as neuregulins) and mental disorders (e.g., schizophrenia, mood disorders, persistent ADHD).
• Adapt circadian models to understand mechanisms responsible for changes in sleep across adolescence.
• Identify neurodevelopmental and endocrine factors mediating changes in impulsivity.
• Identify neurobiological mechanisms responsible for changes in social behavior and play across adolescence.

Unique opportunities for understanding behavioral change in adolescence:

• Develop, adapt, and test appropriate behavioral measures of cognitive and emotional processes for use across the pre-pubertal to adult developmental window in model systems and in humans.
• Utilizing these measures, examine the role of emotional intensity and valence on cognitive function.
• Examine potential interaction of physical changes during puberty with psychological challenges in adjusting to gender role conflicts emerging in adolescence.
• Develop standardized measures to assess the emotional reaction to puberty and its relationship to emerging psychopathology.

Clinical Research Opportunities:

• Design studies to assess the rate and nature of brain changes (structural, functional, metabolic using neuroimaging and other physiological measures, e.g., sleep EEG) across adolescence in within subject designs. Evaluate the relationship between brain changes and indices of pubertal progression in both sexes.
• Evaluate relationships of these changes to behavioral indices of cognition (e.g., cognitive control, executive functions), emotional regulation, and motivation (e.g., reward sensitivity, decision making).
• Assess in clinical populations the effects of alterations of normal temporal patterns of endocrine development on brain function and behavior.
• Evaluate relationships between brain changes that occur in adolescence and genetic determinants of such changes in both healthy development and clinical disorders. Relate such changes to clinical symptoms and to cognitive and emotional functioning.
• Identify pubertal/adolescent "triggers" of clinical disorders, including adolescent onsets of disorder in previously healthy populations, as well as emerging comorbidities in childhood onset disorders (e.g., development of comorbid mood and anxiety disorders in ADHD).
• Identify potential targets for pharmacological and/or psychosocial interventions.
• Characterize mechanisms activated in response to ecological stressors to elucidate the potential impact of acute vs. persistent conditions vs. traumatic events.
• Identify behaviors in adolescence continuous with the later expression of symptoms of mental disorders in adulthood. Determine which behavioral measures are sensitive to change in longitudinal or intervention studies.

The evolution and vitality of the biomedical sciences require a constant infusion of new ideas, techniques, and points of view. These may differ substantially from current thinking or practice and may not yet be supported by substantial preliminary data. By using the R21 mechanism, the NIH seeks to foster the introduction of novel scientific ideas, model systems, tools, agents, targets, and technologies that have the potential to substantially advance biomedical research.

The R21 mechanism is intended to encourage new exploratory and developmental research projects. For example, such projects could assess the feasibility of a novel area of investigation or a new experimental system that has the potential to enhance health-related research. Another example could include the unique and innovative use of an existing methodology to explore a new scientific area. These studies may involve considerable risk but may lead to a breakthrough in a particular area, or to the development of novel techniques, agents, methodologies, models, or applications that could have a major impact on a field of biomedical, behavioral, or clinical research.

Applications for R21 awards should describe projects distinct from those supported through the traditional R01 mechanism. For example, long-term projects, or projects designed to increase knowledge in a well-established area, will not be considered for R21 awards. Applications submitted under this mechanism should be exploratory and novel. These studies should break new ground or extend previous discoveries toward new directions or applications. Projects of limited cost or scope that use widely accepted approaches and methods within well established fields are better suited for the R03 small grant mechanism. Information on the R03 program can be found at http://grants.nih.gov/grants/funding/r03.htm.

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information

1. Mechanism of Support

This FOA will use the NIH Exploratory/Developmental Research Grant (R21) award mechanism. As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

This FOA uses just-in-time concepts. It also uses the modular budget formats (see the Modular Applications and Awards section of the NIH Grants Policy Statement. Specifically, if you are submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities and Administrative [F&A] costs), use the PHS398 Modular Budget component provided in the SF424 (R&R) Application Package and SF424 (R&R) Application Guide (see specifically Section 5.4, Modular Budget Component, of the Application Guide).

Exploratory/developmental grant support is for new projects only; competing renewal (formerly competing continuation ) applications will not be accepted. Up to two resubmissions (formerly revisions/amendments") of a previously reviewed exploratory/developmental grant application may be submitted. See NOT-OD-03-041, May 7, 2003.

2. Funds Available

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the Institutes and Centers (ICs) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications.

The total project period for an application submitted in response to this funding opportunity may not exceed 2 years. Although the size of award may vary with the scope of research proposed, it is expected that applications will stay within the budgetary guidelines for an exploratory/developmental project; direct costs are limited to $275,000 over an R21 two-year period, with no more than $200,000 in direct costs allowed in any single year. Applicants may request direct costs in $25,000 modules, up to the total direct costs limitation of $275,000 for the combined two-year award period. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this funding opportunity announcement.

Facilities and Administrative (F&A) costs requested by consortium participants are not included in the direct cost limitation. See NOT-OD-05-004.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

You may submit an application(s) if your organization has any of the following characteristics:

• For-profit organizations
• Non-profit organizations
• Public or private institutions, such as universities, colleges, hospitals, and laboratories
• Units of State government
• Units of Local government
• Eligible agencies of the Federal government
• Domestic institutions/organizations
• Foreign institutions/organizations
• Faith-based or community-based organizations
• Indian/Native American Tribal Government (Federally Recognized)
• Indian/Native American Tribal Government (Other than Federally Recognized)
• Indian/Native American Tribally Designated Organizations

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

2. Cost Sharing or Matching

This program does not require cost sharing as defined in the current NIH Grants Policy Statement.

3. Other-Special Eligibility Criteria

Applicants may submit more than one application, provided each application is scientifically distinct.

Section IV. Application and Submission Information

To download a SF424 (R&R) Application Package and SF424 (R&R) Application Guide for completing the SF424 (R&R) forms for this FOA, link to http://www.grants.gov/Apply/ and follow the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both:

• Grants.gov (http://www.grants.gov/GetStarted) and
• eRA Commons (http://era.nih.gov/ElectronicReceipt/preparing.htm)

PD/PIs should work with their institutions/organizations to make sure they are registered in the eRA Commons.

Several additional separate actions are required before an applicant institution/organization can submit an electronic application, as follows:

1) Organizational/Institutional Registration in Grants.gov/Get Started

• Your organization will need to obtain a Data Universal Number System (DUNS) number and register with the Central Contractor Registration (CCR) as part of the Grants.gov registration process.
• If your organization does not have a Taxpayer Identification Number (TIN) or Employer Identification Number (EIN), allow for extra time. A valid TIN or EIN is necessary for CCR registration.
• The CCR also validates the EIN against Internal Revenue Service records, a step that will take an additional one to two business days.
• Direct questions regarding Grants.gov registration to:
  Grants.gov Customer Support
  Contact Center Phone: 800-518-4726
  Business Hours: M-F 7:00 a.m. - 9:00 p.m. Eastern Time
  Email [email protected]

2) Organizational/Institutional Registration in the eRA Commons

• To find out if an organization is already Commons-registered, see the "List of Grantee Organizations Registered in NIH eRA Commons.
• Direct questions regarding the Commons registration to:
  eRA Commons Help Desk
  Phone: 301-402-7469 or 866-504-9552 (Toll Free)
  TTY: 301-451-5939
  Business hours M-F 7:00 a.m. 8:00 p.m. Eastern Time
  Email [email protected]

3) Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.

• The individual designated as the PD/PI on the application must also be registered in the NIH eRA Commons. It is not necessary for PDs/PIs to register with Grants.gov.
• The PD/PI must hold a PD/PI account in the Commons and must be affiliated with the applicant organization. This account cannot have any other role attached to it other than the PD/PI.
• This registration/affiliation must be done by the Authorized Organization Representative/Signing Official (AOR/SO) or their designee who is already registered in the Commons.
• Both the PD/PI and AOR/SO need separate accounts in the NIH eRA Commons since both are authorized to view the application image.

Note that if a PD/PI is also an NIH peer-reviewer with an Individual DUNS and CCR registration, that particular DUNS number and CCR registration are for the individual reviewer only. These are different than any DUNS number and CCR registration used by an applicant organization. Individual DUNS and CCR registration should be used only for the purposes of personal reimbursement and should not be used on any grant applications submitted to the Federal Government.

Several of the steps of the registration process could take four weeks or more. Therefore, applicants should immediately check with their business official to determine whether their organization/institution is already registered in both Grants.gov and the Commons. The NIH will accept electronic applications only from organizations that have completed all necessary registrations.

1. Request Application Information

Applicants must download the SF424 (R&R) application forms and SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

Note: Only the forms package directly attached to a specific FOA can be used. You will not be able to use any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA), although some of the "Attachment" files may be useable for more than one FOA.

For further assistance, contact GrantsInfo: Telephone 301-710-0267, Email: [email protected].

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Prepare all applications using the SF424 (R&R) application forms and in accordance with the SF424 (R&R) Application Guide (MS Word or PDF).

The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH. There are fields within the SF424 (R&R) application components that, although not marked as mandatory, are required by NIH (e.g., the Credential log-in field of the Research & Related Senior/Key Person Profile component must contain the PD/PI’s assigned eRA Commons User ID). Agency-specific instructions for such fields are clearly identified in the Application Guide. For additional information, see Tips and Tools for Navigating Electronic Submission on the front page of Electronic Submission of Grant Applications.

The SF424 (R&R) application is comprised of data arranged in separate components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/APPLY will include all applicable components, required and optional. A completed application in response to this FOA will include the following components:

Required Components:
SF424 (R&R) (Cover component)
Research & Related Project/Performance Site Locations
Research & Related Other Project Information
Research & Related Senior/Key Person
PHS398 Modular Budget

PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist

Optional Components:
PHS398 Cover Letter File

Note: While both budget components are included in the SF424 (R&R) forms package, the NIH R21 uses ONLY the PHS 398 Modular Budget. (Do not use the detailed Research & Related Budget.)

Foreign Organizations

Several special provisions apply to applications submitted by foreign organizations:

• Charge back of customs and import fees is not allowed.
• Format: Every effort should be made to comply with the format specifications, which are based upon a standard U.S. paper size of 8.5 x 11 within each PDF.
• Funds for up to 8% administrative costs (excluding equipment) may be requested. See NOT-OD-01-028, March 29, 2001.
• Organizations must comply with Federal/NIH policies on human subjects, animals, and biohazards.
• Organizations must comply with Federal/NIH biosafety and biosecurity regulations. See Section VI.2., Administrative and National Policy Requirements.
• Additional information regarding foreign grants is available in the NIH Grants Policy Statement (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part12.htm#_Toc54600260).

Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources.

3. Submission Dates and Times

See Section IV.3.A for details.

3.A. Submission, Review, and Anticipated Start Dates

Opening Date: May 19, 2006 (Earliest date an application may be submitted to Grants.gov).
Application Submission Date(s): Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm
Peer Review Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Council Review Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Earliest Anticipated Start Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward

3.A.1. Letter of Intent

A letter of intent is not required for the funding opportunity.

3.B. Submitting an Application Electronically to the NIH

To submit an application in response to this FOA, applicants should access this FOA via http://www.grants.gov/Apply and follow steps 1-4. Note: Applications must only be submitted electronically. PAPER APPLICATIONS WILL NOT BE ACCEPTED.

3.C. Application Processing

Applications may be submitted on or after the opening date and must be successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization) on the application submission/receipt date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the receipt date(s) and time, the application may be delayed in the review process or not reviewed.

Once an application package has been successfully submitted through Grants.gov, any errors have been addressed, and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two business days to view the application image.

• If everything is acceptable, no further action is necessary. The application will automatically move forward for processing by the Division of Receipt and Referral, Center for Scientific Review, NIH, after two business days.
• Prior to the submission deadline, the AOR/SO can Reject the assembled application and submit a changed/corrected application within the two day viewing window. This option should be used if the AOR/SO determines that warnings should be addressed. Reminder: warnings do not stop further application processing. If an application submission results in warnings (but no errors) it will automatically move forward after two business days if no action is taken. Please remember that some warnings may not be applicable or may need to be addressed after application submission.
• If the two day window falls after the submission deadline, the AOR/SO will have the option to Reject the application if, due to an eRA Commons or Grants.gov system issue, the application does not correctly reflect the submitted application package (e.g., some part of the application was lost or didn t transfer correctly during the submission process). The AOR/SO should first contact the eRA Commons Helpdesk to confirm the system error, document the issue, and determine the best course of action. NIH will not penalize the applicant for an eRA Commons or Grants.gov system issue.
• If the AOR/SO chooses to Reject the image after the submission deadline for a reason other than an eRA Commons or Grants.gov system failure, a changed/corrected application still can be submitted but it will be subject to the NIH late policy guidelines and may not be accepted. The reason for this delay should be explained in the cover letter attachment.
• Both the AOR/SO and PD/PI will receive e-mail notifications when the application is rejected or the application automatically moves forward in the process after two days.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Incomplete applications will not be reviewed.

There will be an acknowledgement of receipt of applications from Grants.gov and the Commons. Information related to the assignment of an application to a Scientific Review Group is also in the Commons.

The NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial merit review unless the applicant withdraws the pending application. The NIH will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of an application already reviewed with substantial changes, but such application must include an Introduction addressing the previous critique. Note such an application is considered a "resubmission" for the SF424 (R&R).

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-Award Costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See the NIH Grants Policy Statement.

6. Other Submission Requirements

The NIH requires the PD/PI to fill in his/her Commons User ID in the PROFILE Project Director/Principal Investigator section, Credential log-in field of the Research & Related Senior/Key Person Profile component. The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see Tips and Tools for Navigating Electronic Submission on the front page of Electronic Submission of Grant Applications.

Renewal (formerly competing continuation or Type 2 ) applications are not permitted.

All application instructions outlined in the SF424 (R&R) Application Guide (MS Word or PDF) are to be followed, with the following requirements for R21 applications:

• R21 applications will use the modular budget format and "Just-in-Time" concepts, with direct costs requested in $25,000 modules, up to the total direct costs limitation of $275,000 over an R21 two-year period. No more than $200,000 in direct costs will be allowed in any single year.
• Items 2-5 of the Research Plan of the R21 application may not exceed 15 pages, including tables, graphs, figures, diagrams, and charts.
• Introduction (required for a resubmission application) is limited to one page.
• Preliminary data are not required but may be included if available.
• R21 appendix materials should be limited, as is consistent with the exploratory nature of the R21 mechanism. The following materials may be included in the appendix.
  • Up to five publications, manuscripts (accepted for publication), abstracts, patents, or other printed materials directly relevant to this project. Do not include manuscripts submitted for publication.
    • Publications in press: Include only a publication list with a link to the publicly available on-line journal article or the PubMed Central (PMC) submission identification number. Do not include the entire article.
    • Manuscripts accepted for publication but not yet published: The entire article may be submitted electronically as a PDF attachment.
    • Manuscripts published but a publicly available online journal link is not available: The entire article may be submitted electronically as a PDF attachment.
• Surveys, questionnaires, data collection instruments, clinical protocols, and informed consent documents.
• Graphic images of gels, micrographs, etc. provided that the image (may be reduced in size) is also included within the 15-page limit of Items 2-5 of the Research Plan. No images may be included in the Appendix that are not also represented within the Research Plan.
• Do not use the Appendix to circumvent the page limitations of the Research Plan. An application that does not observe these limitations may be delayed in the review process.

Warning: Please be sure that you observe the direct cost, project period, and page number limitations specified above for this FOA. Application processing may be delayed or the application may be rejected if it does not comply with these requirements.

Note: While each section of the Research Plan needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to better monitor formatting requirements such as page limits. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.

Plan for Sharing Research Data

The precise content of the data-sharing plan will vary, depending on the data being collected and how the investigator is planning to share the data. Applicants who are planning to share data may wish to describe briefly the expected schedule for data sharing, the format of the final dataset, the documentation to be provided, whether or not any analytic tools also will be provided, whether or not a data-sharing agreement will be required and, if so, a brief description of such an agreement (including the criteria for deciding who can receive the data and whether or not any conditions will be placed on their use), and the mode of data sharing (e.g., under their own auspices by mailing a disk or posting data on their institutional or personal website, through a data archive or enclave). Investigators choosing to share under their own auspices may wish to enter into a data-sharing agreement. References to data sharing may also be appropriate in other sections of the application.

Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each Non-Competing Grant Progress Report (PHS 2590). See Section VI.3., Reporting.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.

2. Review and Selection Process

Applications submitted for this funding opportunity will be assigned to the ICs on the basis of established PHS referral guidelines.

Appropriate scientific review groups convened in accordance with the standard NIH peer review procedures (http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific and technical merit.

As part of the initial merit review, all applications will:

• Undergo a selection process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed and assigned a priority score.
• Receive a written critique.
• Receive a second level of review by the appropriate national advisory council or board.

Applications submitted in response to this funding opportunity will compete for available funds with all other recommended applications. The following will be considered in making funding decisions:

• Scientific merit of the proposed project as determined by peer review.
• Availability of funds.
• Relevance to program priorities.

The NIH R21 exploratory/developmental grant is a mechanism for supporting novel scientific ideas or new model systems, tools, or technologies that have the potential to significantly advance our knowledge or the status of health-related research. Because the Research Plan is limited to 15 pages, an exploratory/developmental grant application need not have extensive background material or preliminary information as one might normally expect in an R01 application. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Reviewers will place less emphasis on methodological details and certain indicators traditionally used in evaluating the scientific merit of R01 applications, including supportive preliminary data. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application.

Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?

Innovation: Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?

Investigators: Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the PD/PI and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?

Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

2.A. Additional Review Criteria:

In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the priority score:

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed. See item 6 of the Research Plan component of the SF424 (R&R).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated. See item 7 of the Research Plan component of the SF424 (R&R).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five items described under item 11 of the Research Plan component of the SF424 (R&R) will be assessed.

Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

2.B. Additional Review Considerations

Budget and Period of Support: The reasonableness of the proposed budget and the appropriateness of the requested period of support in relation to the proposed research may be assessed by the reviewers. Is the percent effort listed for the PD/PI appropriate for the work proposed? Is each budget category realistic and justified in terms of the aims and methods?

2.C. Sharing Research Data

Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data may be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The funding organization will be responsible for monitoring the data sharing policy. http://grants.nih.gov/grants/policy/data_sharing.

2.D. Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

Program staff will be responsible for the administrative review of the plan for sharing research resources.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each Non-Competing Grant Progress Report (PHS 2590), See Section VI.3., Reporting.

Model Organism Sharing Plan: Reviewers are asked to assess the sharing plan in an administrative note. The sharing plan itself should be discussed after the application is scored. Whether a sharing plan is reasonable can be determined by the reviewers on a case-by-case basis, taking into consideration the organism, the timeline, the applicant's decision to distribute the resource or deposit it in a repository, and other relevant considerations. For the R21 mechanism, the presence or adequacy of a plan should not enter into the scoring of the application.

3. Anticipated Announcement and Award Dates

Not Applicable

Section VI. Award Administration Information

1. Award Notices

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the NIH eRA Commons.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See Section IV.5., Funding Restrictions.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities.

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

Section VII. Agency Contacts

We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues:

1. Scientific/Research Contacts:

Questions regarding scientific/research issues about basic neuroscience related to normal adolescent brain biology including cellular and molecular neurobiology, developmental neuroendocrinology, systems neurobiology, basic behavioral research, and tool and ligand development may be directed to:

Lois Winsky, Ph.D.
Division of Neuroscience and Basic Behavioral Science
National Institute of Mental Health
6001 Executive Blvd, Room 7184, MSC 9641
Bethesda, MD 20892-9641
Telephone: (301) 443-5288
FAX: (301) 402-4740
Email: [email protected]

Questions regarding scientific/research issues related to human neuroimaging and behavioral studies or questions relevant to susceptibility or resilience to mental disorders in adolescence may be directed to:

Judith Rumsey, Ph.D.
Division of Pediatric Translational Research and Treatment Development
National Institute of Mental Health
6001 Executive Blvd, Room 6180, MSC 9617
Bethesda, MD 20892-9617
Telephone: (301) 443-9264
FAX: (301) 402-9876
Email: [email protected]

2. Peer Review Contacts:

Not Applicable

3. Financial or Grants Management Contacts:

Dawn Walker
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Boulevard, Room 6112, MSC 9605
Bethesda, MD 20892-9605
Telephone: (301) 443-3858
FAX: (301) 443-6885
Email: [email protected]

Section VIII. Other Information

Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protection:
Federal regulations (45 CFR 46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants ( NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement). Beginning October 1, 2004, all investigators submitting an NIH application or contract proposal are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the SF424 (R&R) application; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research. Applications that do not provide this information will be returned without review.

NIH Public Access Policy:
NIH-funded investigators are requested to submit to the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov) at PubMed Central (PMC) an electronic version of the author's final manuscript upon acceptance for publication, resulting from research supported in whole or in part with direct costs from NIH. The author's final manuscript is defined as the final version accepted for journal publication, and includes all modifications from the publishing peer review process.

NIH is requesting that authors submit manuscripts resulting from 1) currently funded NIH research projects or 2) previously supported NIH research projects if they are accepted for publication on or after May 2, 2005. The NIH Public Access Policy applies to all research grant and career development award mechanisms, cooperative agreements, contracts, Institutional and Individual Ruth L. Kirschstein National Research Service Awards, as well as NIH intramural research studies. The Policy applies to peer-reviewed, original research publications that have been supported in whole or in part with direct costs from NIH, but it does not apply to book chapters, editorials, reviews, or conference proceedings. Publications resulting from non-NIH-supported research projects should not be submitted.

For more information about the Policy or the submission process, please visit the NIH Public Access Policy Web site at http://publicaccess.nih.gov/ and view the Policy or other Resources and Tools, including the Authors' Manual.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This PA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.

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